Previously it was demonstrated that host nerve fibers could successfully regenerate through a 4 cm length of nerve allograft that contained minor antigens provided that the host rat was rendered immunologically tolerant to the transplantation antigens of the nerve donor. A similar result has presently been obtained in tolerant rats grafted with nerves that bore the more highly antigenic major as well as minor antigens. However, after tolerance was abolished (by injecting lymphoid cells already sensitized to allograft antigens) in rats with successful nerve allografts, rejection occurred and host nerve fibers in the graft degenerated and disappeared. Although tolerance induction is an experimental model of immunosuppression, the results indicate that the prevention of rejections is the main barrier to overcome when allografts are needed to repair injured peripheral nerve. An evaluation of currently available immunosuppressive drugs have revealed that Cyclosporin-A is the most effective in preventing nervous tissue rejection.